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Randomized Controlled Trial
. 2023 Aug 1;80(8):824-832.
doi: 10.1001/jamaneurol.2023.2094.

Safety and Efficacy of Tenecteplase Compared With Alteplase in Patients With Large Vessel Occlusion Stroke: A Prespecified Secondary Analysis of the ACT Randomized Clinical Trial

Fouzi Bala  1   2 , Nishita Singh  1   3 , Brian Buck  4 , Ayoola Ademola  1   5 , Shelagh B Coutts  1   5   6   7 , Yan Deschaintre  8   9 , Houman Khosravani  10 , Ramana Appireddy  11 , Francois Moreau  12 , Stephen Phillips  13 , Gord Gubitz  13 , Aleksander Tkach  14 , Luciana Catanese  15 , Dar Dowlatshahi  16 , George Medvedev  17 , Jennifer Mandzia  18 , Aleksandra Pikula  19 , Jai Jai Shankar  20 , Heather Williams  21 , Thalia S Field  22 , Alejandro Manosalva Alzate  23 , Muzaffar Siddiqui  24 , Atif Zafar  25 , Oje Imoukhoude  26 , Gary Hunter  27 , Ibrahim Alhabli  1 , Faysal Benali  1   28 , MacKenzie Horn  1 , Michael D Hill  1   5   6   7 , Michel Shamy  16 , Tolulope T Sajobi  1   5 , Richard H Swartz  10 , Bijoy K Menon  1   5   6   7 , Mohammed Almekhlafi  1   5   6   7
Affiliations
Randomized Controlled Trial

Safety and Efficacy of Tenecteplase Compared With Alteplase in Patients With Large Vessel Occlusion Stroke: A Prespecified Secondary Analysis of the ACT Randomized Clinical Trial

Fouzi Bala et al. JAMA Neurol. .

Abstract

Importance: It is unknown whether intravenous thrombolysis using tenecteplase is noninferior or preferable compared with alteplase for patients with acute ischemic stroke.

Objective: To examine the safety and efficacy of tenecteplase compared to alteplase among patients with large vessel occlusion (LVO) stroke.

Design, setting, and participants: This was a prespecified analysis of the Intravenous Tenecteplase Compared With Alteplase for Acute Ischaemic Stroke in Canada (ACT) randomized clinical trial that enrolled patients from 22 primary and comprehensive stroke centers across Canada between December 10, 2019, and January 25, 2022. Patients 18 years and older with a disabling ischemic stroke within 4.5 hours of symptom onset were randomly assigned (1:1) to either intravenous tenecteplase or alteplase and were monitored for up to 120 days. Patients with baseline intracranial internal carotid artery (ICA), M1-middle cerebral artery (MCA), M2-MCA, and basilar occlusions were included in this analysis. A total of 1600 patients were enrolled, and 23 withdrew consent.

Exposures: Intravenous tenecteplase (0.25 mg/kg) vs intravenous alteplase (0.9 mg/kg).

Main outcomes and measures: The primary outcome was the proportion of modified Rankin scale (mRS) score 0-1 at 90 days. Secondary outcomes were an mRS score from 0 to 2, mortality, and symptomatic intracerebral hemorrhage. Angiographic outcomes were successful reperfusion (extended Thrombolysis in Cerebral Infarction scale score 2b-3) on first and final angiographic acquisitions. Multivariable analyses (adjusting for age, sex, National Institute of Health Stroke Scale score, onset-to-needle time, and occlusion location) were carried out.

Results: Among 1577 patients, 520 (33.0%) had LVO (median [IQR] age, 74 [64-83] years; 283 [54.4%] women): 135 (26.0%) with ICA occlusion, 237 (45.6%) with M1-MCA, 117 (22.5%) with M2-MCA, and 31 (6.0%) with basilar occlusions. The primary outcome (mRS score 0-1) was achieved in 86 participants (32.7%) in the tenecteplase group vs 76 (29.6%) in the alteplase group. Rates of mRS 0-2 (129 [49.0%] vs 131 [51.0%]), symptomatic intracerebral hemorrhage (16 [6.1%] vs 11 [4.3%]), and mortality (19.9% vs 18.1%) were similar in the tenecteplase and alteplase groups, respectively. No difference was noted in successful reperfusion rates in the first (19 [9.2%] vs 21 [10.5%]) and final angiogram (174 [84.5%] vs 177 [88.9%]) among 405 patients who underwent thrombectomy.

Conclusions and relevance: The findings in this study indicate that intravenous tenecteplase conferred similar reperfusion, safety, and functional outcomes compared to alteplase among patients with LVO.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Coutts reports that Boehringer Ingelheim provides the study drug (tenecteplase) for the TEMPO-2 trial that Dr Coutts is principal investigator of. Dr Catanese received payments from Servier, consulting fees from Ischaemaview RAPID, Circle NVI, and Canadian Medical Protective Association. Dr Shankar has a grant from Medtronic paid to the University of Manitoba. Dr Field reports grants from Bayer Canada and personal fees from Roche Canada, HLS Therapeutics, and AstraZeneca outside the submitted work. Dr Hill reports grants from Alberta Innovates QuICR Program (used in part for the ACT trial) and from Canadian Institutes for Health Research paid to the University of Calgary for the ACT trial during the conduct of the study as well as grants from Boehringer Ingelheim paid to the University of Calgary for the TEMPO-2 trial, from Biogen, Medtronic, and NoNO Inc paid to the University of Calgary outside the submitted work; in addition, Dr Hill has US patents 62/086 077 and 10 916 346 licensed to Circle, Inc; paid work from Sun Pharma for adjudication of clinical trial outcomes; a consulting relationship with Brainsgate for clinical trial design; and serves as president of the Canadian Neurological Sciences Federation (not-for-profit sector). Dr Sajobi has received consulting fees from Circle NVI. Dr Swartz has stock options in FollowMD and gets salary support for research from the Heart & Stroke Foundation of Canada, the Sandra Black Centre for Brain Resilience & Recovery, and Ontario Brain Institute. Dr Menon has stock options in Circle NVI and has consulted for Biogen and Boehringer Ingelheim. Dr Almekhlafi reports grants from Canadian Institute of Health Research during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Distribution of Modified Rankin Scale (mRS) Scores at 90 to 120 Days
There was no significant difference between the tenecteplase and alteplase groups in the ordinal analysis of the mRS score, adjusted for age, sex, baseline stroke severity, occlusion location, and time from stroke symptom onset to needle as fixed-effects variables and site as a random-effects variable (adjusted common odds ratio, 0.91; 95% CI, 0.66-1.23). The mRS score ranges from 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability, 2 slight disability, 3 moderate disability, 4 moderately severe disability, 5 severe disability, and 6 death.
Figure 2.
Figure 2.. Forest Plot of Adjusted Risk Ratio (RR) for the Clinical and Procedural Outcomes Stratified by Vessel Occlusion Location
Clinical outcomes (modified Rankin scale [mRS] score 0-1 and mRS 0-2) were adjusted for age, sex, baseline stroke severity, occlusion location, and time from stroke symptom onset to needle time as fixed-effects variables and site as a random-effects variable. Procedural outcomes were adjusted for age as a fixed-effects variable and site as a random-effects variable. P values for interaction were not significant for all outcomes (P > .05). BA indicates basilar artery; eTICI, expanded thrombolysis in cerebral infarction; ICA, intracranial internal carotid artery; M1-MCA, first segment of middle cerebral artery; M2-MCA, second segment of the middle cerebral artery; rAOL, revised arterial occlusion scale.
See this image and copyright information in PMC

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